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Type II transmembrane domain hydrophobicity dictates the cotranslational dependence for inversion.

Dou D, da Silva DV, Nordholm J, Wang H, Daniels R - Mol. Biol. Cell (2014)

Bottom Line: Membrane insertion by the Sec61 translocon in the endoplasmic reticulum (ER) is highly dependent on hydrophobicity.Overall the cotranslational inversion of marginally hydrophobic NA TMDs initiates once ~70 amino acids past the TMD are synthesized, and the efficiency reaches 50% by ~100 amino acids, consistent with the positioning of this TMD class in type II human membrane proteins.Inversion of the M2 TMD, achieved by elongating its C-terminus, underscores the contribution of cotranslational synthesis to TMD inversion.

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Nin-Cout (type II) NA TMDs from human H1N1 IAVs have a broad hydrophobicity range. (A) Topologies for the IAV membrane proteins NA, HA, and M2 and how their TMD positioning influences ribosomal involvement during the membrane integration step. (B) Dot plot showing predicted hydrophobicity (ΔGapp) variation in the unique NA, HA, and M2 TMDs from human H1N1 IAV sequences. Note that TMD hydrophobicity decreases with increasing positive ΔGapp.
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Figure 1: Nin-Cout (type II) NA TMDs from human H1N1 IAVs have a broad hydrophobicity range. (A) Topologies for the IAV membrane proteins NA, HA, and M2 and how their TMD positioning influences ribosomal involvement during the membrane integration step. (B) Dot plot showing predicted hydrophobicity (ΔGapp) variation in the unique NA, HA, and M2 TMDs from human H1N1 IAV sequences. Note that TMD hydrophobicity decreases with increasing positive ΔGapp.

Mentions: The analysis of protein sequence homology, property, and structural conservation has proved extremely useful in identifying protein topology and localization, functional domains, and the existence of certain cellular machinery (von Heijne, 2006; Daniels et al., 2010). However, the limited number of homologous sequences for human single-spanning membrane protein has hindered these approaches. Therefore we used the extensive human influenza A virus (IAV) sequence database to perform a comparative analysis of the TMD characteristics from natural single-spanning membrane proteins with Nout-Cin (HA and M2) and Nin-Cout (NA) orientations (Figure 1A).


Type II transmembrane domain hydrophobicity dictates the cotranslational dependence for inversion.

Dou D, da Silva DV, Nordholm J, Wang H, Daniels R - Mol. Biol. Cell (2014)

Nin-Cout (type II) NA TMDs from human H1N1 IAVs have a broad hydrophobicity range. (A) Topologies for the IAV membrane proteins NA, HA, and M2 and how their TMD positioning influences ribosomal involvement during the membrane integration step. (B) Dot plot showing predicted hydrophobicity (ΔGapp) variation in the unique NA, HA, and M2 TMDs from human H1N1 IAV sequences. Note that TMD hydrophobicity decreases with increasing positive ΔGapp.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214783&req=5

Figure 1: Nin-Cout (type II) NA TMDs from human H1N1 IAVs have a broad hydrophobicity range. (A) Topologies for the IAV membrane proteins NA, HA, and M2 and how their TMD positioning influences ribosomal involvement during the membrane integration step. (B) Dot plot showing predicted hydrophobicity (ΔGapp) variation in the unique NA, HA, and M2 TMDs from human H1N1 IAV sequences. Note that TMD hydrophobicity decreases with increasing positive ΔGapp.
Mentions: The analysis of protein sequence homology, property, and structural conservation has proved extremely useful in identifying protein topology and localization, functional domains, and the existence of certain cellular machinery (von Heijne, 2006; Daniels et al., 2010). However, the limited number of homologous sequences for human single-spanning membrane protein has hindered these approaches. Therefore we used the extensive human influenza A virus (IAV) sequence database to perform a comparative analysis of the TMD characteristics from natural single-spanning membrane proteins with Nout-Cin (HA and M2) and Nin-Cout (NA) orientations (Figure 1A).

Bottom Line: Membrane insertion by the Sec61 translocon in the endoplasmic reticulum (ER) is highly dependent on hydrophobicity.Overall the cotranslational inversion of marginally hydrophobic NA TMDs initiates once ~70 amino acids past the TMD are synthesized, and the efficiency reaches 50% by ~100 amino acids, consistent with the positioning of this TMD class in type II human membrane proteins.Inversion of the M2 TMD, achieved by elongating its C-terminus, underscores the contribution of cotranslational synthesis to TMD inversion.

View Article: PubMed Central - PubMed

Show MeSH
Related in: MedlinePlus